RESUMO

The renin-angiotensin system (RAS) is comprised of a series of peptides, receptors, and enzymes that play a pivotal role in maintaining cardiovascular homeostasis. Among the most important players in this system are the Angiotensin-II and Angiotensin-(1-7) peptides. Our group has recently demonstrated that alamandine (ALA), a peptide with structural and functional similarities to Angiotensin-(1-7), interacts with cardiomyocytes, enhancing contractility via the Mas-related G protein-coupled receptor member D (MrgD). It is currently unknown whether this modulation varies along the distinct phases of the day. To address this issue, we assessed the ALA-induced contractility response of cardiomyocytes from mice at four Zeitgeber times (ZTs). At ZT2 (light phase), ALA enhanced cardiomyocyte shortening in an MrgD receptor-dependent manner, which was associated with NO production. At ZT14 (dark phase), ALA induced a negative modulation on the cardiomyocyte contraction. ß-Alanine, an MrgD agonist, reproduced the time-of-day effects of ALA on myocyte shortening. L-NG-Nitroarginine Methyl Ester (L-NAME), an NO synthase inhibitor, blocked the increase in fractional shortening induced by ALA at ZT2. No effect of ALA on myocyte shortening was observed at ZTs 8 and 20. Our results show that ALA/MrgD signaling in cardiomyocytes is subject to temporal modulation. This finding has significant implications for pharmacological approaches that combine chronotherapy for cardiac conditions triggered by disruption of circadian rhythms and hormonal signaling.

RESUMO

OBJECTIVE: Our study aimed to revaluate the significant data from meta-analyses on genetic variations in immune mediators and the risk of prostate cancer (PCa) by Bayesian approaches. METHODS: We performed a search on the literature before September 5th, 2023, for meta-analytic studies on polymorphisms in immune mediator genes and the risk of PCa. Two Bayesian approaches were used to assess the level of noteworthiness in the meta-analytic data: the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. The quality evaluation of studies was performed with the Venice criteria. Gene-gene and protein-protein networks were designed for the genes and products enrolled in the results. RESULTS: As results, 18 meta-analyses on 17 polymorphisms in several immune mediator genes were included (IL1B rs16944/rs1143627, IL4 rs2243250/rs2227284/rs2070874, IL6 1800795/rs1800796/rs1800797, IL8 rs4073, IL10 rs1800896/rs1800871/rs1800872, IL18 rs1946518, COX2 rs2745557, TNFA rs361525 and PTGS2 rs20417/689470). The Bayesian calculations showed the rs1143627 and the rs1946518 polymorphisms in IL1B and IL18 genes, respectively, were noteworthy. The Venice criteria showed that only four studies received the highest level of evidence. The gene-gene and protein-protein networks reinforced the findings on IL1B and IL18 genes. CONCLUSION: In conclusion, this current Bayesian revaluation showed that the rs1143627 and the rs1946518 polymorphisms in the IL1B and IL18 genes, respectively, were noteworthy biomarker candidates for PCa risk.

Assuntos

RESUMO

The fall armyworm (Spodoptera frugiperda), a polyphagous insect pest, is a major threat to food production, rapidly spreading through all the tropical areas in the world. Resistance has developed to the control protocols used so far (pyrethroids, organophosphorus, and genetically modified plants), and alternative strategies must be found. The bioactivity in essential oils is usually associated with the major constituents, but synergistic interactions among the constituents (even minor ones) can improve the levels of activity considerably. Herein, we tested the insecticidal activity of several constituents of the essential oil from Piper aduncum, an Amazonian Piperaceae, both separately and as binary mixtures, through their application on the dorsal side of the larva pronotum. Dillapiole proved to be, isolated, the most active compound in this oil (LD50 = 0.35 ppm). In binary mixtures, a strong synergistic effect was observed for the pairs of dillapiole with ß-caryophyllene (LD50 = 0.03 ppm), methyl eugenol (LD50 = 0.05 ppm), and α-humulene (LD50 = 0.05 ppm). In some cases, however, antagonism was recorded, as for dillapiole + ß-pinene (LD50 = 0.44 ppm). The use of binary mixtures of essential oil constituents as low-environmental-toxicity insecticides allows a fine tuning of the insecticidal activity, and the exploitation of synergy effects.

RESUMO

AIMS: The consumption of highly refined carbohydrates increases systemic inflammatory markers, but its potential to exert direct myocardial inflammation is uncertain. Herein, we addressed the impact of a high-refined carbohydrate (HC) diet on mice heart and local inflammation over time. MAIN METHODS: BALB/c mice were fed with a standard chow (control) or an isocaloric HC diet for 2, 4, or 8 weeks (HC groups), in which the morphometry of heart sections and contractile analyses by invasive catheterization and Langendorff-perfused hearts were assessed. Cytokines levels by ELISA, matrix metalloproteinase (MMP) activity by zymography, in situ reactive oxygen species (ROS) staining and lipid peroxidation-induced TBARS levels, were also determined. KEY FINDINGS: HC diet fed mice displayed left ventricular hypertrophy and interstitial fibrosis in all times analyzed, which was confirmed by echocardiographic analyses of 8HC group. Impaired contractility indices of HC groups were observed by left ventricular catheterization, whereas ex vivo and in vitro indices of contraction under isoprenaline-stimulation were higher in HC-fed mice compared with controls. Peak levels of TNF-α, TGF-ß, ROS, TBARS, and MMP-2 occur independently of HC diet time. However, a long-lasting local reduction of the anti-inflammatory cytokine IL-10 was found, which was linearly correlated to the decline of systolic function in vivo. SIGNIFICANCE: Altogether, the results indicate that short-term consumption of HC diet negatively impacts the balance of anti-inflammatory defenses and proinflammatory/profibrotic mediators in the heart, which can contribute to HC diet-induced morphofunctional cardiac alterations.

Assuntos

RESUMO

Hepatocellular carcinoma (HCC) is considered as the second cause of cancer-related deaths worldwide. Genetic variations are associated with HCC risk, an issue that has been the subject of several meta-analyses. However, meta-analyses have an important limitation on the likelihood of false positive data. Henceforth, this study aimed to assess the level of noteworthiness in the meta-analyses by means of a Bayesian approach. A systematic search was performed for meta-analyses with associations between gene polymorphisms and HCC. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-5. The quality of studies was evaluated by the Venice criteria. As additional analyses, the gene-gene and protein-protein networks were designed for these genes and products. As results, we found 33 meta-analytic studies on 45 polymorphisms occurring in 35 genes. A total of 1,280 values for FPRP and BFDP were obtained. Seventy-five for FPRP (5.86%) and 95 for BFDP (14.79%) were noteworthy. In conclusion, the polymorphisms in CCND1, CTLA4, EGF, IL6, IL12A, KIF1B, MDM2, MICA, miR-499, MTHFR, PNPLA3, STAT4, TM6SF2, and XPD genes were considered as noteworthy biomarkers for HCC risk.

Assuntos

RESUMO

The insecticidal effect of the essential oil of Piper aduncum (EOPA), and of its constituent dillapiole [1-allyl-2,3-dimethoxy-4,5- (methylenedioxy) benzene] in particular, is well documented in the literature and can be associated with its interference with the enzymatic detoxification in arthropods. However, no data exist on the range of dillapiole content associated with insecticidal activity, which is necessary to establish reliable dose-activity parameters for a formulated product. The oil composition can also change during storage after distillation, mainly due to environmental factors such as light incidence, atmospheric oxygen and temperature, which can be deleterious to oil quality. In this study, EOPA subjected to different storage conditions over four years and its rectified fractions were submitted to bioassays to evaluate their insecticidal effect by topical contact and residual contact against Spodoptera frugiperda. Our objectives were to determine the relationship between dillapiole content and the insecticidal activity of EOPA, and to evaluate its chemical and toxicological properties over time under different conditions. Our results showed that EOPA was stable with respect to the dillapiole content and the toxicological effect against S. frugiperda under different storage conditions for four years. The overall chemical composition of the EOPA did not vary significantly among storage conditions. EOPA with dillapiole content ranging between 68% and 100% showed greater insecticidal toxicity by residual and topical contact against S. frugiperda larvae.(AU)

O efeito inseticida do óleo essencial de Piper aduncum (OEPA) e, particularmente, de seu constituinte dilapiol [1-alil-2,3- dimetoxi-4,5-(metilenodioxi) benzeno], está bem documentado na literatura e pode estar associado à sua interferência na desintoxicação enzimática em artrópodes. No entanto, não existem dados sobre a amplitude de teores de dilapiol associados à atividade inseticida, o que é necessário para estabelecer parâmetros de dose-atividade confiáveis para um produto formulado. A composição do óleo também pode sofrer alterações durante seu armazenamento após a destilação, principalmente devido a fatores ambientais como incidência de luz, oxigênio atmosférico e temperatura, que podem ser deletérios à qualidade do óleo. Neste estudo, durante quatro anos, OEPA submetido a diferentes condições de armazenamento e suas frações retificadas foram submetidos a bioensaios para avaliar seu efeito inseticida por contato tópico e contato residual contra Spodoptera frugiperda. Nossos objetivos foram determinar a relação entre o teor de dilapiol e a atividade inseticida do OEPA, e avaliar suas propriedades químicas e toxicológicas ao longo do tempo sob diferentes condições. Nossos resultados mostraram que o OEPA foi estável em relação ao teor de dilapiol e o efeito toxicológico contra S. frugiperda sob diferentes condições de armazenamento durante quatro anos. A composição química do OEPA não variou significativamente entre as condições de armazenamento. OEPA com teor de dilapiol entre 68% e 100% apresentou maior toxicidade inseticida por contato residual e tópico contra larvas de S. frugiperda.(AU)

Assuntos

RESUMO

Congenital Zika syndrome (CZS) constitutes a recently identified malformation caused by Zika virus infection during pregnancy. Limited data is available to date on the facial dysmorphic features of these patients. This study evaluated the facial dysmorphisms of children with CZS, compared with clinically healthy children, using clinical examination and standardized photographic images. Sixty-three children with CZS (9.70 ± 3.2 months-age), and 31 Controls (8.67 ± 6.2 months-age) joined the study. Seven out of 15 indices differed between groups: midfacial height (MFH)/horizontal facial reference (HFR) (p = .0003), interalar distance/HFR (p = .0027), nasal root depth/MFH (p = .0030), posterior nasal length/MFH (p = .0002), vertical position of the ear/MFH (p <.0001), ear length/MFH (p = .0005), chin height/total facial height (CH/TFH) (p <.0001). A CH/TFH of 0.229 showed 93.9% sensitivity and 80.6% specificity in diagnosing CZS. Children with CZS had broad, short faces, decreased intercanthal distance, short posterior nasal length, prominent nasal root, broad nasal wings, and high-set and long ears. Increased chin height index provided the most accurate diagnostic potential.

Assuntos

RESUMO

Background: In horses, an increase in the volume of penis and foreskin can be caused by trauma. The resultant edema interferes with the retraction of the penis and cause paraphimosis. Surgical intervention through penectomy is indicated in cases wherein an alternative treatment is not feasible. Partial penectomy can prolong the life and reproductive function of many stallions. The present study aims to report on the methodological, functional, and economic feasibility of a successful case of the use of Williams technique for partial penectomy performed in the field in a horse with paraphimosis, preserving urinary, productive, and reproductive functions. Case: A 10-year-old horse weighing 500 kg had clinical signs of paraphimosis due to the formation of granulomatous tissue following trauma to the glans region. A surgical intervention, namely a partial penectomy was decided to be performed to prevent injury from priapism. Due to the limited resources provided by the owner and the impossibility of moving the animal to a surgical center in a veterinary hospital, the procedure was performed in the field, with prior sanitization and preparation of the environment used to perform surgery. The horse was tranquilized with intravenous xylazine hydrochloride and acepromazine, with subsequent induction of anesthesia with ready-to-use (RTU) guaifenesin bolus and maintenance of anesthesia with an intravenous association of RTU guaifenesin, xylazine hydrochloride, and ketamine. The distal third of the penis was amputated using the recommended Williams technique. Although the complications like dehiscence and emergence of granulation tissue occurred after surgery, these were controlled in the daily follow-up of the animal and post-surgical treatment. Discussion: Paraphimosis predisposed the horse to abrasions and edema of the exposed portion of the penis. However, there was no urine retention, which suggested that the urethral ostium and the urethra had no lesions. Because the granulomatous lesions were located in the distal third of the penis and the extent of penile exposure was small, the partial penectomy technique proved effective in solving the permanent exposure of the penis. The anesthetic protocol used was inexpensive, easy to execute, and effective, and no anesthetic complications occurred, proving this protocol to be efficient for the anesthetic induction of animals in the field. In addition to being reliable and widespread, the Williams technique was recommended to prevent possible urethral stenosis and the development of contact dermatitis by urine. This technique makes a rapid recovery of the animal possible, with improvement of its physiological parameters, and due to ease of being able to be done in the field, it is also inexpensive. The edema and the granulation tissue that occurred after surgery were controlled with medication. In general, post-penectomy animals are not used for reproduction. This makes the present report an important contribution, because in cases in which the lesions present a distal disposition and the penile exposure is small, stallions have a chance of maintaining reproductive function after surgery, even with a long period of evolution before surgical treatment. This was demonstrated in the present case, as the animal in this case later impregnated a mare, with the pregnancy confirmed by ultrasound examination. Partial penectomy is a resolution technique for cases of traumatic paraphimosis, in which exuberant granulation tissue is formed in the distal third of the penis, with a long period of evolution. The surgery can be done in the field, with a low surgical cost to the owner, and a good productive and reproductive prognosis for the animal.

Assuntos

RESUMO

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca2+ dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca2+ spark rate and enhanced Ca2+ reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca2+ transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.

Assuntos

RESUMO

Mammalian carnivores are considered a key group in maintaining ecological health and can indicate potential ecological integrity in landscapes where they occur. Carnivores also hold high conservation value and their habitat requirements can guide management and conservation plans. The order Carnivora has 84 species from 8 families in the Neotropical region: Canidae; Felidae; Mephitidae; Mustelidae; Otariidae; Phocidae; Procyonidae; and Ursidae. Herein, we include published and unpublished data on native terrestrial Neotropical carnivores (Canidae; Felidae; Mephitidae; Mustelidae; Procyonidae; and Ursidae). NEOTROPICAL CARNIVORES is a publicly available data set that includes 99,605 data entries from 35,511 unique georeferenced coordinates. Detection/non‐detection and quantitative data were obtained from 1818 to 2018 by researchers, governmental agencies, non‐governmental organizations, and private consultants. Data were collected using several methods including camera trapping, museum collections, roadkill, line transect, and opportunistic records. Literature (peerreviewed and grey literature) from Portuguese, Spanish and English were incorporated in this compilation. Most of the data set consists of detection data entries (n = 79,343; 79.7%) but also includes non‐detection data (n = 20,262; 20.3%). Of those, 43.3% also include count data (n = 43,151). The information available in NEOTROPICAL CARNIVORES will contribute to macroecological, ecological, and conservation questions in multiple spatio‐temporal perspectives. As carnivores play key roles in trophic interactions, a better understanding of their distribution and habitat requirements are essential to establish conservation management plans and safeguard the future ecological health of Neotropical ecosystems. Our data paper, combined with other largescale data sets, has great potential to clarify species distribution and related ecological processes within the Neotropics. There are no copyright restrictions and no restriction for using data from this data paper, as long as the data paper is cited as the source of the information used. We also request that users inform us of how they intend to use the data.